1. Field of the Invention
The present invention relates to methods and apparati for the precise positioning of cells in a selected array or pattern on a separable substratum. More specifically, the invention relates to methods and apparati for preparing tissues, and in particular, human tissues, having a precisely controlled cellular organization.
2. Description of the Related Art
The ability to prepare organized tissues or tissue-like structures starting with individual cells or colonies of cells is a science that is still in its infancy. However, tissue and even organ culture has progressed to a point such that it is now possible to routinely layer individual cells or colonies of most any particular cell type or types onto an appropriate solid matrix, and grow the layered cells in an appropriate medium until a randomly organized "tissue" is obtained. Although such tissues have a potentially wide range of usefulness, their primary utility has been in the field of tissue transplantation or replacement, for example, in plastic surgery and tissue reconstruction.
Tissue reconstruction employing tissues formed from cultured cells has found its most widespread application in the context of burn patient treatment. Traditionally, the treatment of burn victims has consisted primarily of debridgement of the dead tissue, maintaining a sterile moist environment around the affected area, and allowing the body to produce scar tissue While effective under optimal circumstances, such treatments suffer from potentially serious drawbacks due to the difficulty in maintaining the affected area in a sterile, moist environment. This inability can lead to serious repercussions such as severe infection, the leading cause of death in burn patients who survive the initial burn trauma.
More recently, attempts have been made to improve the treatment of burn patients through the use of a sterile layer of skin tissue that is grown in vitro and transplanted to cover the burned tissue. Such transplanted tissues serve the dual purpose of both protecting the affected area, by providing a physical barrier to infection, as well as aiding in maintaining the burned tissue in a humidified state. In such methods, cultures of freshly explanted dermis, preferably from the affected patient to be treated, are prepared by explanting dermal tissue, dissociating the tissue into individual cells, and culturing the dissociated cells in vitro to form a "tissue" layer. Once an integral tissue layer is obtained, it is transplanted to the burn patient to cover the affected area. While certain problems are addressed by this technique, including in particular, problems associated with tissue rejection, the method nevertheless has serious drawbacks. Most notable of these drawbacks is the inability to precisely structure and organize the cultured tissue in that many cell types are randomly positioned with respect to each other. Accordingly, the normal arrangement of cells in a normal tissue is generally not reproduced in the grafted tissue which can lead to a grafted tissue that is not normal in appearance, often colorless or blotched.
Accordingly, there is currently a need for novel approaches to the construction of transplantable tissues or tissue-like structure which would allow the precise positioning of cells into organized tissue structures for subsequent transplantation. Moreover, there is a need to provide techniques and apparati which allow the orderly and reproducible formation of transplantable tissues into structures suitable for application to burn victims, for the production of synthetic veins or even organs, or other medical uses.